SANGRE DE GRADO

Technical Data Report for

SANGRE DE GRADO “Dragon's Blood” (Croton lechleri)

© Copyrighted 2002 - 2007. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage or retrieval system, without written permission.

This document is not intended to provide medical advice and is sold with the understanding that the publisher and the author are not liable for the misconception or misuse of information provided. The author shall have neither liability nor responsibility to any person or entity with respect to any loss, damage, or injury caused or alleged to be caused directly or indirectly by the information contained in this document or the use of any plants mentioned. Readers should not use any of the products discussed in this document without the advice of a medical professional.

© Copyrighted 2002 and updated 2007 by Leslie Taylor, ND., 3579 Hwy 50 East, Suite 222, Carson City, NV 89701. All rights reserved.

Sangre de Grado "Dragon's Blood"

Reprinted from the book The Healing Power of Rainforest Herbs © Copyrighted 2005 by Dr. Leslie Taylor, ND and Square One Publishers, Inc.

Family: Euphorbiaceae Genus: Croton Species: lechleri, salutaris Synonyms: Croton draco Common Names: Sangre de grado, sangre de drago, dragon’s blood, drago, sangue de drago, sangue de agua Parts Used: Bark, resin/sap

Herbal Properties & Actions Main Actions:

Other Actions:

Standard Dosage: Re sin

heals wounds

kills cancer cells

Internal: 10-15 drops twic e daily

stops bleeding

prev ents tum or growth

Extern al: Apply to affected area

kills bacte ria

stops cellular mutations

twic e daily

kills germ s kills fungi kills viruses relieves diarrhea reduces inflamm ation relieves itching

Sangre de grado is a medium to large-sized tree that grows from 10–20 m high in the upper Amazon region of Peru, Ecuador, and Colombia. Although tall, the trunk is usually less than 30 cm in diameter and is covered by smooth, mottled bark. It has large, heart-shaped, bright green leaves and unique, greenish-white flowers on long stalks. Its Peruvian name, sangre de grado, means “blood of the dragon” (in Spanish). In Ecuador, it’s named sangre de drago (which means “dragon’s blood” as well). When the trunk of the tree is cut or wounded, a dark red, sappy resin oozes out as if the tree is bleeding—earning this local name. The genus Croton is a large one, with 750 species of trees and shrubs distributed across the tropical and subtropical regions of both hemispheres. Crotons are rich in active alkaloids, and several species are well-known medicinal plants used as laxatives and tonics. TRIBAL AND HERBAL MEDICINE USES Sangre de grado’s red sap or latex (and also its bark) has a long history of indigenous use in the rainforest and in South America. The earliest written reference dates its use to the 1600s, when Spanish naturalist and explorer P. Bernabé Cobo found that the curative power of the sap was widely known throughout the indigenous tribes of Mexico, Peru, and Ecuador. For centuries, the sap has been painted on wounds to staunch bleeding, to accelerate healing, and to seal and protect injuries from infection. The sap dries quickly and forms a barrier, much like a “second skin.” It is used externally by indigenous tribes and local people in Peru for wounds, fractures, and hemorrhoids, internally for intestinal and stomach ulcers, and as a douche for vaginal discharge. Other indigenous uses include treating intestinal fevers and inflamed or infected gums, in vaginal baths before and after childbirth, for hemorrhaging after childbirth, and for skin disorders. 1

Sangre de grado resin and bark are used in traditional medicine in South America today in much the same manner as indigenous ones. In Peruvian herbal medicine, it is recommended for hemorrhaging, as an antiseptic vaginal douche and, topically, for healing wounds. It is also used internally for ulcers in the mouth, throat, intestines, and stomach; as an antiviral for upper respiratory viruses, stomach viruses, and HIV; internally and externally for cancer and, topically, for skin disorders, insect bites, and stings. In Brazilian traditional medicine, the sap currently is used for wounds, hemorrhaging, diarrhea, mouth ulcers, and as a general tonic. PLANT CHEMICALS Sangre de grado resin or sap is a storehouse of phytochemicals, including proanthocyanidins (antioxidants), simple phenols, diterpenes, phytosterols, and biologically active alkaloids and lignans. Scientists have attributed many of the biologically active properties of the sap (especially its wound-healing capacity) to two main “active” constituents: an alkaloid named taspine,and a lignan named dimethylcedrusine. Of course, botanists, herbalists, and naturopaths would disagree with such reductionist conclusions (and often do); in this particular case, the matter is actually proven by science. Noted author and ex-USDA economic botanist Dr. James Duke summed this up eloquently, saying, I like the comments on dragon’s blood, and would add one further note: in addition to the proanthocyanadins (including Pycnogenol) and taspines, there’s another active ingredient—dimethylcedrusine. While each of these alone—dimethylcedrusine, Pycnogenol and taspine—was shown to effectively heal wounded rats (with squares of skin exfoliated, i.e., peeled off) by European scientists, the whole dragon’s blood was shown to speed healing four times faster. The whole was better than the sum of its parts. Synergy makes the whole herb stronger; diversity makes the rainforest stronger.1 The taspine alkaloid from sangre de grado was first documented with antiinflammatory actions in 1979.2 In 1985, taspine was documented with antiinflammatory, antitumorous (against sarcomas), and antiviral actions.3 The main plant chemicals in sangre de grado include alpha-calacorene, alpha-copaene, alphapinene, alpha-thujene, beta-caryophyllene, beta-elemene, beta-pinene, betaine, bincatriol, borneol, calamenene, camphene, catechins, cedrucine, crolechinic acid, cuparophenol, D-limonene, daucosterol, dihydrobenzofuran, dimethylcedrusine, dipentene, eugenol, euparophenol, gallocatechin, gamma-terpinene, gamma-terpineol, hardwickiic acid, isoboldine, korberin A and B, lignin, linalool, magnoflorine, methylthymol, myrcene, norisoboldine, p-cymene, proanthocyanidins, procyanidins, resin, tannin, taspine, terpinen-4-ol, and vanillin. BIOLOGICAL ACTIVITIES AND CLINICAL RESEARCH The wound-healing action of sangre de grado resin was first related to the taspine alkaloid in 1989.4 Several later studies also concentrated on the wound-healing5 and antitumorous properties of taspine.6 The lignan dimethylcedrusine was isolated by scientists in 1993 and was shown to play a central role in sangre de grado’s effective wound-healing action.7 This Belgian study revealed that the crude resin stimulated contraction of wounds, helped in the formation of a crust/scab at the wound site, regenerated skin more rapidly, and assisted in the formation of new collagen. This was the study to which Dr. Duke referred in documenting that the crude resin was found to be four times more effective at wound healing and collagen formation than its isolated chemicals (and healed wounds ten to twenty times faster than using nothing at all).7 The Belgian scientists also determined that taspine was active against herpes virus in this 2

study. In 1994 other phytochemicals were found, including phenolic compounds, proanthocyanadins, and diterpenes, which showed potent antibacterial activity (against E. coli and Bacillus subtilis) as well as wound-healing properties.8 Another study documented sangre de grado’s antioxidant effects9 and researchers in Canada documented its antifungal properties.10 Another important traditional use of the sap was verified by clinical research in a 2000 study designed to evaluate its gastrointestinal effects. Researchers concluded that “Sangre de grado is a potent, cost-effective treatment for gastrointestinal ulcers and distress via antimicrobial, antiinflammatory, and sensory afferent-dependent actions.”11 In 2002, these same researchers reported that sangre de grado evidenced an in vitro effect against stomach cancer and colon cancer cells as well.12 In 2003, Italian researchers reported that the resin inhibited the growth of a human myelogenous leukemia cell line and also prevented cells from mutating in test tube studies.13 Extracts of sangre de grado have demonstrated antiviral activity against influenza, parainfluenza, herpes simplex viruses I and II, and hepatitis A and B.7, 8,14,15 The antiviral and antidiarrhea properties of sangre de grado have come to the attention of the pharmaceutical industry over the last ten years. A U.S.-based pharmaceutical company has filed patents on three pharmaceutical preparations that contain antiviral constituents and novel chemicals (a group of plant flavonoids they’ve named SP-303), extracted from the bark and resin of sangre de grado. Their patented drugs include an oral product for the treatment of respiratory viral infections, a topical antiviral product for the treatment of herpes, and an oral product for the treatment of persistent diarrhea. These products have been the subject of various human clinical trials. Although the immunomodulating effects of sangre de grado have not been the subject of targeted research yet, some researchers believe that the anti-inflammatory, antimicrobial, and antioxidant activities may provide nonspecific immune enhancement effects as well.16 More recently, several scientific tests have been conducted on a proprietary sangre de grado product (made into a skin balm), which was also based on traditional uses. They reported that in pest control workers, a sangre de grado balm was preferred over placebo, for the relief of itching, pain, discomfort, swelling, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and allergic plant reactions (poison ivy and others).17 Subjects reported relief within minutes, and that it provided pain relief and alleviated symptoms (itching and swelling) for up to six hours. These reported effects in humans, as well as several other tests they conducted in animals and in vitro models of inflammation, led them to conclude that sangre de grado prevents pain sensation by blocking the activation of nerve fibers that relay pain signals to the brain (therefore functioning as a broad-acting pain killer), as well as blocking the tissue response to a chemical released by nerves that promotes inflammation. CURRENT PRACTICAL USES Research has confirmed many of the indigenous uses of this powerful rainforest plant. It is a wonderful, sustainable rainforest resource that warrants consumer attention as it becomes more widely available in the marketplace. Applied directly to the affected area, it is helpful for all types of cuts, scrapes, external wounds, bites, stings, rashes, and skin problems, including skin and nail fungi. James E. Williams, OMD, sums up sangre de grado’s many uses by natural health practitioners, stating: There is a wide range of potential applications for sangre de grado, including as a broadspectrum anti-diarrheal agent from causes such as side effects of drugs, chemotherapy or radiation treatment, microbial infections of the intestine, traveler’s diarrhea, and viralinduced diarrhea as in AIDS. It may also have other uses in gastrointestinal disorders such as irritable bowel syndrome and ulcerative diseases. Its cytotoxic effects make it a possible antitumor agent and its cicatrizant properties provide wound-healing potential. In addition, the antimicrobial and anti-inflammatory effects of sangre de grado make it a 3

useful compound in the clinical treatment of chronic viral diseases and as a natural antibacterial agent.15 In addition, several health practitioners in the U.S. indicate benefits in using sangre de grado resin internally for diabetic neuropathy because of its previously documented effects on nerve endings, nerve pain, and nerve inflammation. Benefits have also been reported with diabetesrelated skin ulcers and sores (applied topically), which have refused to heal using other methods. TRADITIONAL PREPARATION For external use, the resin/sap is rubbed directly on the affected area several times daily and allowed to dry. Please note: the resin is red! It will temporarily stain the skin a reddish-brown (which will wash off), but it will permanently stain clothing. Rubbing the resin in the palm of the hand first or directly where applied will thicken the resin into a thin, lighter colored paste, which helps form a second skin on top of a wound or rash and reduces staining. For internal use, the traditional remedy is 10–15 drops in a small amount of liquid, taken one to three times daily (be prepared, however; it tastes quite dreadful). Contraindications: None reported. Drug Interactions: None reported.

Worldwide Ethnomedical Uses Region

Uses

Brazil

for bacterial infections, blood cleansing, cancer, digestive disorders, fever, fungal infections, hemorrhages, stomach ulcers, tumors, ulcer (mouth), wounds, and for its astringent (drying) effects

Dominican Republic

for wounds, and to stop bleeding

Ecuador

for cancer, inflammation, wounds

Mexico

for fever, infected gums, wounds

Peru

for cancer, diabetes, diarrhea, eczema, fractures, fungal infections, gastrointestinal problems, hemorrhages, hemorrhoids, infected gums, infections, insect bites, laryngitis, rheumatism, skin cancer, skin rashes, throat problems, toothache, tumors, ulcers (intestinal, mouth, stomach), vaginal discharge, vaginal infections, vaginitis, wounds, and as an antiseptic

United States

for cancer, diabetic neuropathy, eczema, fungal infections (skin, nail, foot), hemorrhages, inflammation, insect bites, itching, pain, rashes, ulcers (intestinal, mouth, skin, stomach), wounds, and as an antiseptic

4

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

14. 15.

16.

Duke, James A. “Added Comments on the Rainforest” Whole Foods Magazine, May 1997. Perdue, G. P., et al. “South American plants II: Taspine isolation and anti-inflammatory activity.” J. Pharm. Sci. 1979; 68(1): 124–26. Vlietinck, A. J. and R. A. Dommisse, eds. Advances in Medicinal Plant Research. Stuttgart: Wiss. Verlag, 1985. Vaisberg, A. J., et al. “Taspine is the cicatrizant principle in sangre de grado extracted from Croton lechleri.” Planta Med. 1989; 55(2): 140–43. Porras-Reyes, B. H., et al. “Enhancement of wound healing by the alkaloid taspine defining mechanism of action.” Proc. Soc. Exp. Biol. Med. 1993; 203(1): 18–25. Itokawa, H., et al. “A cytotoxic substance from sangre de grado.” Chem. Pharm. Bull. (Tokyo) 1991; 39(4): 1041–42. Pieters, L., et al. “Isolation of a dihydrobenzofuran lignan from South American dragon’s blood (Croton sp.) as an inhibitor of cell proliferation.” J. Nat. Prod. 1993; 56(6): 899–906. Chen, Z. P., et al. “Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon’s blood.” Planta Med. 1994; 60(6): 541–45. Desmarchelier, C., et al. “Effects of sangre de drago from Croton lechleri Muell.-Arg. on the production of active oxygen radicals.” J. Ethnopharmacol. 1997; 58: 103–8. Macrae, W. D., et al. “Studies on the pharmacological activity of Amazonian Euphorbiaceae.” J. Ethnopharmacol. 1988; 22(2): 143–72. Miller, M. J., et al. “Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado.” Am. J. Physiol. Gastrointest. Liver Physiol. 2000; 42: G192–200. Sandoval, M., et al. “Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells.” J. Ethnopharmacol. 2002; 80(2-3): 121–9. Meza E. N., ed. Desarrollando Nuestra Diversidad Biocultural: “Sangre de Grado" y el Reto de su Producción Sustentable en el Perú. Lima: Universidad Nacional Mayor de San Marcos; 1999. Sidwell R., et al. “Influenza virus-inhibitory effects of intraperitoneally and aerosoladministered SP-303, a plant flavonoid.” Chemotherapy 1994; 40(1): 42–50. Williams, J. E. “Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado.” Altern. Med. Rev. 2001; 6(6): 567–79. Miller, M. J., et al. “Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado.” J. Invest. Dermatol. 2001; 117(3): 725–30.

The information contained herein is intended for education, research, and informational purposes only. This information is not intended to be used to diagnose, prescribe or replace proper medical care. The statements contained herein have not been evaluated by the Food and Drug Administration. The plant described herein is not intended to diagnose, treat, cure, mitigate, or prevent any disease.

5

Ethnomedical Information on Sangre de Grado (Croton lechleri) Plant Part / Location

Docum ented Ethnic Use

Type Extract / Rou te

Used For

Ref #

Latex Am azo nia

Used externally for wounds, taken internally for intestinal fevers and pyorrhea.

Latex / Various

Hum an Adult

AS1003

Latex Am azo nia

Taken orally in hot water to hasten internal healing following an abortion. Used to stop bleeding and heal wounds. Used as a vaginal douche after childbirth. Used for tuberculoisis and bone ca ncer.

Latex Latex Latex Latex

/ Oral / External / Douche / Oral

Hum an Adult

ZZ1011

Latex Am azo nia

Used for wound healing. Used for internal inflamm ation, ulcers and cance r.

Latex / External Latex / Oral

Hum an Adult

ZZ2007

Latex Brazil

Used to treat wounds and as a protection against bacterial and fungal infections to wounds.

Latex / External

Hum an Adult

ZZ1099

Latex Brazil

Used for wounds, hemorrhaging, mouth ulcers and a general tonic.

Latex / Oral & External

Hum an Adult

ZZ1013

Latex Ecuador

Used for inflamm ation and the treatment of wounds.

Latex / External

Hum an Adult

H11766

Latex Ecuador

Used for cancer.

Latex / External & Oral

Hum an Adult

H11766

Latex Peru

Used as a cicatrizant and hemostat for wounds. Used for stomach, liver and uterine cancers, and stomach ulcers. Three drops of resin in a coca leaf tea with salt used for tonsilitis and sore throa t. Resin mixed in a bath with Llanten herb used for vaginal infections and gonorrhea.

Latex / External Latex / Internal Latex / Gargle

Hum an Adult

ZZ2009

Latex Peru

Used for wound healing, in baths before childbirth.

Latex / External

Hum an Adult

L04137

Latex Peru

Used for stomach ulcers.

Latex / Oral

Hum an Adult

L04137

Latex Peru

Used as an anti-inflamm atory and vulnerary to heal wounds. Considered astringent, a ntio xidant, an tivira l, anti-tum oral, antiinflamm atory, antiangiogenic, and anti-cancerous.

Latex / External Latex / External & Oral

Hum an Adult

ZZ2013

Latex Peru

Used topically on skin cance r.

Latex / External

Hum an Adult

H22027

6

Late x / Ba th

Plant Part / Location



Used For

Ref #

Latex Peru

Used for rheumatism.

Latex / Oral

Hum an Adult

N00002

Latex Peru

Used for cancer.

Latex / Oral

Hum an Adult

K10718

Latex Peru

Used to improve gastrointestinal function, to protect the mucous mem brane lining of the lower gastrointestinal tract, and to treat diarrhea.

Latex / Oral

Hum an Adult

AS1002

Latex Peru

Used as an oral gargle for sore throat, as a vaginal antiseptic after childbirth, topically as a hemostatic, and taken internally for wound healing.

Latex / Various

Hum an Adult

AS1002

Latex Peru

Used for for hemorrhaging, as an antiseptic vaginal douche, for wounds, and ulcers in the mouth, throat and stomach.

Latex / Oral

Hum an Adult

ZZ1008

Latex Peru

Used for sore throat and laryngitis, toothaches, menstrual hemorrhages.

Latex / Oral

Hum an Adult

ZZ1093

Latex Peru

Used for stomach and intestinal ulcers.

Latex / Oral

Hum an Adult

ZZ1045

Latex Peru

Used for wounds, leucorrhea, fractures and piles.

Latex / External

Hum an Adult

ZZ1041

Latex Peru

Used for wound healing.

Latex / External

Hum an Adult

K10718

Latex Peru

Used for wounds and sk in cancer. Used for cancer, high blood pressure, sore throat, infections, and diabetes.

Latex / External

Hum an Adult

ZZ1084

Latex Peru

Used Used Used Used

Latex / External Latex / External Infusion / Douche Latex / Oral

Hum an Adult

ZZ1101

Latex Peru Bark P eru

Considered cicatrizant, antiulcerous, anti-inflamm atory, anti-tumorous, and anticancerous. Used for internal and external wounds and ulcers, for tuberculosis, cancer, urogenital disorders, internal and external inflamm ation, uterine disorders and inflamm ation, and mouth and throat inflamm ation, soreness and infections.

Latex / Oral & External and Bark Decoction / Oral

Hum an Adult

ZZ2012

Latex Peru

Used as a cicatrizant (forms sc abs) and vulnerary (heals wounds). Used for hemorrhoids, leucorrhea, fractures, a vaginal wash after childbirth, stomach ulcers, and rheumatic swellings.

Latex / External Latex / Oral or External

Hum an Adult

ZZ1105

as a cicatrizant for wounds. for fractures and rheu m atism (to reduc e pain and inflam m ation). as a vaginal wash after childbirth. for stomach ulcers.

7

Latex / Oral

Plant Part / Location



Used For

Ref #

Latex Peru

Peruvian ethnobiologist, Nicola Bautista Monardes (1493-1588) recorded Peruvian Indians using the latex medicinally in a 1580 publication.

Latex / Not stated

Hum an Adult

AS1011

Latex South America

Used as a cicatrizan t, an ti-inflam m ato ry, hem ostat, and antitu m oral. Used for cuts, wounds, and skin ulcers.

Latex / Not stated Latex / External

Hum an Adult

AC1010

Latex South America

Used for diarrhea, wounds, tumors, stomach ulcers, herpes infection, and insect bites.

Latex External & Oral

Hum an Adult

L26272

Leaf+B ark Pe ru

A cold maceration of leaves and bark are used by various indigenous tribes in the Peruvian A m azon for bloody urine and clots in the bladder.

Maceration / Oral

Hum an Adult

AS1010

Leaves Peru

Fresh leaves are chewed to fortify the teeth and for toothaches.

Leaves / Oral

Hum an Adult

ZZ1093

Leaves Brazil

Considered depurative, febrifuge and stomachic.

H2O extract / Oral

Hum an Adult

ZZ1099

8

Presence of Compounds in Sangre de Grado (Croton lechleri) Compound

Chemical Type

Plan t Part

Plan t Origin

Benzen e, 1-3 -5-trim etho xy:

Benzenoid

Bark Sap Sap

Ecuad or Ecuad or Ecuad or

Qu antity

Ref #

0.0024%

H11766 K18768 H11766

Be nzo furan-5-yl,2-3-dihydro: 2-(3 -dim eth oxy-phenyl): 7-m eth oxy-3-m eth oxycarbonyl-propan-1-oic acid methyl ester

Lignan

Sap

Brazil

K10718

Be nzo furan-5-yl,2-3-dihydro:2 -(4-hydroxy-3-m eth oxy-phenyl)-7-m eth oxy3-methoxy-carbonyl-propen-1-oic acid methyl ester

Lignan

Sap

Brazil

K10718

Be nzyl a lcohol, 3-4-dim eth oxy:

Benzenoid

Bark Sap

Ecuad or Ecuad or

0.0008%

Bin catriol

Diterpene

Bark Sap

Ecuad or Ecuad or

Boldine, iso

Alk aloid

Sap Sap Leaf Leaf

Peru Ecuador Peru Ecuador

AS1001 AS1001 AS1001 AS1001

Boldine, nor, iso

Alk aloid

Sap Sap Leaf Leaf


AS1001 AS1001 AS1001 AS1001

Cate chin (4 -alpha-8)-gallocatec hin (4-alpha-6)- gallocatec hin

Flavonoid

Latex

Ecuad or

Cate chin (4 -alpha-8)-gallocatec hin (4-alpha-8)-gallocatec hin

Flavonoid

Latex

Ecuad or

Catech in, (+):

Flavonoid

Latex Sap Latex

Ecuador Ecuad or Ecuad or

00.04%

H07769 K18768 L26126

Ca tech in, epi: (-):

Flavonoid

Latex Sap Latex


00.038%

H07769 K18768 L26126

9

0.00792%

H11766 H11766

00.09%

H11766 K18768

H07769 H07769

Compound

Chemical Type

Plan t Part

Plan t Origin

Qu antity

Ce drus in, 3'-4-o -dim ethyl:

Lignan

Sap Sap

Peru Peru

00.00136%

Ce drus in, 3'-4-o -dim ethyl: (dl):

Lignan

Sap

Brazil

Ce drus in, 4-o-m ethyl:

Lignan

Sap

Peru

00.00025%

J16430

Crolechinic acid

Diterpene

Bark Sap Sap


00.02943%

H11766 H11766 K18768

Sap Bark

Ecuad or Ecuad or

Bark Sap Sap


00.0028%

H11766 H11766 K18768

Crolechinol

Diterpene

Daucoste rol

Steroid

Ref # J16430 K22608 K10718

00.00717%

K18768 H11766

Gallocatec hin (4-alpha-6)-epi-gallocate chin

Flavonoid

Latex

Ecuad or

00.36%

H07769

Gallocatec hin (4-alpha-8)-epi-catec hin

Flavonoid

Latex

Ecuad or

00.0083%

H07769

Gallocatec hin (4-alpha-8)-gallocatec hin (4-alpha-8)-epi-gallocate chin

Flavonoid

Latex

Ecuad or

00.13%

H07769

Gallocatechin, (+):

Flavonoid

Latex Sap

Ecuad or Ecuad or

Ga llocatechin, epi: (-):

Flavonoid

Latex Sap Latex

Ecuad or Ecuad or Ecuador

Glaucine

Alk aloid

Leaf

Peru

Hardw ick iic acid

Diterpene

Bark Sap

Ecuad or Ecuad or

00.00660%

H11766 K18768

Korberin A

Diterpene

Bark Sap

Ecuad or Ecuad or

00.03584%

H14225 K18768

Korberin B

Diterpene

Bark Sap

Ecuad or Ecuad or

00.03018%

H14225 K18768

10

00.072%

00.085%

H07769 K18768 H07769 K18768 L26126 AS1001

Compound

Chemical Type

Plan t Part

Plan t Origin

Magnoflorine

Alk aloid

Sap Sap Leaf Leaf


AS1001 AS1001 AS1001 AS1001

Phene thyl alcohol, 4-hydroxy:

Benzenoid

Sap Bark Sap


00.032%

K18768 H11766 H11766

Bark Sap

Ecuador Ecuad or

00.0044%

H11766 H11766

Sap Bark Sap


00.0012%

K18768 H11766 H11766

Bark Sap

Ecuad or Ecuad or

00.0014%

H11766 H11766

Phenethyl alcohol, 4-hydroxy: acetate

Benzenoid

Pheno l, 2-4-6-trim etho xy:

Benzenoid

Ph enol, 3-4-dim eth oxy:

Benzenoid

Qu antity

Procyanidin B-1

Flavonoid

Latex Latex

Ecuador Ecuad or

Procyanidin B-2

Flavonoid

Latex

Ecuador

Procyanidin B-4

Flavonoid

Latex Sap

Ecuador Ecuad or

00.073%

H07769 K18768

Sinoacutine

Alk aloid

Leaf

Peru

00.0001%

K28263

Sitostenone, beta:

Steroid

Bark Sap

Ecuad or Ecuad or

00.0018%

H11766 H11766

Sap Bark Sap


00.0054%

K18768 H11766 H11766

Sitosterol, be ta:

Steroid

SB-300

Fla vonoid

Latex

Peru

SP-303

Fla vonoid

Latex Latex Latex

Peru Peru Peru

11

00.046%

Ref #

H07769 L26126 L26126

L26431 01.0%

H14332 L26272 L26431

Compound

Chemical Type

Plan t Part

Plan t Origin

Taspine

Alkaloid

Sap Latex Sap Latex Sap Sap Bark Sap Leaf Latex Latex

Peru Peru Peru Peru Peru Peru Ecuad or Ecuad or Peru Peru Ecuador

Leaf

Peru

Thaliporphine

Alk aloid

12

Qu antity

00.08504% 00.00014%

9.4%

Ref # A14041 W 02272 K22608 M26029 N00002 J16430 H11766 H11766 AS1001 AS1001 L26126 AS1001

Biological Activities for Extracts of Sangre de Grado (Croton lechleri) Part - Origin

Activity Tested For

Type Extract

Test Model

Dosage

Result

Notes/Organism tested

Ref #

Latex Peru

Toxic Effects General

Fresh Latex

PO Mouse & Topical Mouse

Various

Inactive

In a two-stage mouse skin carcinogenesis system neither Latex nor taspine had carcinogenic or tumor promoter activity after 17 months of treatment.

M26029

Latex Peru

Cell Proliferation Activity

Fresh Latex

Cell Culture

Not stated

Inactive

Latex Peru

Cell Proliferation Activity

Fresh Latex

Cell Culture

150 ng/ml

Inactive

vs. human foreskin fibroblasts (Had no effect on cell proliferation.)

M26029

Freeze-dried Latex Ecuador

Antiproliferation Activity

Fresh Latex

Cell Culture

100 mcg/ml

Weak Activity

vs. mitogen stimulated splenocytes and lymphoid leukemia cells

L26126

Latex Peru

Tumor Promoting Activity

Fresh Latex

Cell Culture

Not stated

Inactive


Mutagenic Activity

H20 EXT

Agar Plate

IC50: 50 mcg/plate IC50: 100 mcg/plate IC50: 340 mcg/plate IC50: 430 mcg/plate

Inactive Inactive Active Active

Salmonella typhimurium

L24801

Latex Peru

Mutagenic Activity

H20 EXT

Agar Plate

Various

Weak Activity

Salmonella typhimurium

L27225

Latex Ecuador

Antimutagenic Activity

H20 EXT

Agar Plate

Various

Active

vs. sodium azidr- and 2nitrofluorene- induced mutagenicty

L24801

Dried Trunkbark Ecuador

Cytotoxic Activity

MEOH EXT

Cell Culture

IC50: 50.0 mcg/ml

Weak Activity

vs. CA-9KB

K18768

Heartwood Ecuador

Cytotoxic Activity

MEOH EXT

Cell Culture

IC50: 25.0 mcg/ml

Weak Activity

vs. CA-9KB

K18768

Dried Leaf Ecuador

Cytotoxic Activity

MEOH EXT

Cell Culture

IC50: 90.0 mcg/ml

Weak Activity

vs. CA-9KB

K18768

GI = Gastric Intubation

IG = Intragastric

IP = Intraperitoneally

IV = Intravenously 13

PO = Orally

AS1014

AS1014

SC = Subcutaneously

IM = Intramuscular

Part - Origin

Activity Tested For

Type Extract

Test Model

Dosage

Result


Ref #

Dried Latex Ecuador

Cytotoxic Activity

CHCL3 EXT

Cell Culture

IC50: >900 mcg/ml

Inactive

vs. CA-9KB

K18768

Dried Latex Ecuador

Cytotoxic Activity

MEOH EXT Acetone EXT CHCL3 EXT ETOAC EXT

Cell Culture Cell Culture Cell Culture Cell Culture

IC50: 186.0 mcg/ml IC50: 125.0 mcg/ml IC50: 186.0 mcg/ml IC50: 70.0 mcg/ml

Equiv. Equiv. Equiv. Weak Activity

vs. CA-9KB

K18768


Cytotoxic Activity

H2O EXT

Cell Culture

IC50: 2.5 mcg/ml

Active

vs. Leuk-K562

L24801

Latex Peru

Cytotoxic Activity

Latex

Cell Culture

Not stated

Active

various tumor cell lines

AS1015

Latex Peru

Cytotoxic Activity

Dimethlycedrusine Ext

Cell Cuture

GI50: 0.3 mcg

Active

various tumor cell lines

AS1009

Dried Bark Peru

Crown Gall Tumor Inhibition

ETOAC EXT

Cell Culture

LC50: 1.8 mcg/ml

Active

Assay system is intended to predict for antitumor activity.

T16253

Dried Bark Peru

Crown Gall Tumor Inhibition

H2O EXT

Cell Culture

LC50: 3.0 mcg/ml

Active


T16253

Dried Bark Peru

Anticrustacean Activity

ETOAC EXT

Artemia salina

LC50: 15.2 mcg/ml

Active


T16253

Dried Bark Peru

Anticrustacean Activity

H2O EXT

Artemia salina

LC50: 1000 mcg/ml

Active


T16253

Fresh Latex Brazil

Anticytotoxic Activity

Latex

Cell Culture

Not stated

Active

endothelium-human-umbilical vein (Cells were protected against degradation in a starvation medium.)

K10718

Dried Stembark Ecuador

Cell Differentiation Induction

MEOH EXT

Cell Culture

IC50: 2.3 mcg/ml

Active

LEUK - HL60

L10644


IG = Intragastric



PO = Orally

SC = Subcutaneously

IM = Intramuscular

Part - Origin

Activity Tested For

Type Extract

Test Model

Dosage

Result


Ref #


DNA Synthesis Inhibition

MEOH EXT Acetone EXT CHCL3 EXT ETOAC EXT

Cell Culture Cell Culture Cell Culture Cell Culture

20.0 mcg/ml 20.0 mcg/ml 20.0 mcg/ml 20.0 mcg/ml

Active Inactive Active Active

cells - endothelial

K18768

Fresh Latex Brazil

DNA Synthesis Inhibition

Not stated

Cell Culture

Not stated

Active

endothelium-human-umbilical vein (Cells were protected against degradation in a starvation medium.)

K10718

Fresh Latex Peru

Wound Healing Acceleration

Latex

External Mouse

Not stated

Active

M26029

Latex Peru


Latex Polyphenolic fraction

External Rat External Rat

0.01% 7.0%

Active Active

M26029

Fresh Latex Brazil


Not stated

Not stated

Not stated

Active

K10718


Immunostimulant Activity

Latex

Not stated

5 mcg/ml

Active

Increased phagocytosis in neutrophils.

L26126


Immunostimulant Activity

Latex

Not stated

10 mcg/ml

Active

Increased phagocytosis in monocytes.

L26126

Fresh Latex Peru

Analgesic Activity

Latex

IP Rat

50.0 mcg/animal

Active

Latex Peru

Anti-inflammatory Activity

Taspine fraction

Rat

Various

Active

vs. carrageenan-induced pedal edema, vs cotton pellet-induced granuloma and vs. adjuvant polyarthritis model.

N00002



Latex

IP Rat

5 mg/kg

Active

vs. carrageenan-induced pedal edema

L26126

Fresh Latex Peru


Latex

IP Rat

500 mcg/animal

Active


Antiulcerous Activity

Latex

Not stated

IC50: 5 mcg/ml

Active


Antioxidant Activity

Latex

Cell Culture

IC50: 7.73 mcg/ml

Active


IG = Intragastric



PO = Orally

L16482

L16482 vs. prednisolone-induced ulcers

SC = Subcutaneously

L26126 L26126

IM = Intramuscular

Part - Origin

Activity Tested For

Type Extract

Test Model

Dosage

Result


Ref #

Latex Peru


Latex

In vitro

Not stated

Active

Scavenged free radicals, reduced lipid peroxidation and mediated free radical mediated DNA damage.

AS1012

Latex Peru


Latex

Cell Culture

Various

Active

vs. apomorphine-induced oxidative damage in Saccharomyces cerevisiae

L27225

Fresh Latex Peru

Hemostatic Activity

Latex

Rat

1%

Active

vs. mucosa (gastric)

L16482

Fresh Latex Peru

Vasorelaxation Activity

Latex

Rat

Not stated

Active

Artery

L16482

Fresh Latex Peru


Lyophilized EXT

Not stated

IC50: 1.0 mcg/ml

Active

Freeze-dried Latex Peru

CNS Depressant Activity

Latex

IG Mouse

ED50: 88.35 mg/kg

Active

vs. exploratory assay

L04841


Antidiarrheal Activity

Isolated favonoids SB-300 & SP-303

Cell Culture

Not stated

Active

Inhibited CFTR-mediated chloride secretion in human colonic epithelial cells.

L26431


Antibacterial Activity

Acetone EXT

Agar Plate

MIC: 30.0 mcg/disc

Weak Activity

Bacillus subtilis Escherichia coli

K18768



CHCL3 EXT

Agar Plate

MIC: 0.08 mcg/disc MIC: 10.0 mcg/disc

Active Active


K18768



ETOAC EXT

Agar Plate

MIC: 50.0 mcg/disc

Weak Activity


K18768



MEOH EXT

Agar Plate

MIC: 10.0 mcg/disc

Active


K18768

Dried Bark Peru


ETOAC EXT

Agar Plate

1.0 mg/disc

Active Inactive

Staphylococcus aureus Escherichia coli

T16253

Dried Bark Peru


H2O EXT

Agar Plate

1.0 mg/disc

Inactive Inactive

Staphylococcus aureus Escherichia coli

T16253

Latex Colombia


H2O EXT

Agar Plate

1.0 mg/disc

Active

Staphylococcus aureus

AS1013


IG = Intragastric



PO = Orally

J19239

SC = Subcutaneously

IM = Intramuscular

Part - Origin

Activity Tested For

Type Extract

Test Model

Dosage

Result


Ref #

Dried Bark Peru

Antifungal Activity

ETOAC EXT

Agar Plate

0.25 mg/ml 0.13 mg/ml 0.13 mg/ml Not stated

Active Active Active Inactive

Trichophytum gallinae Microsporum canis Microsporum gypseum Microsporum fulvum

T16253

Dried Bark Peru

Antifungal Activity

H2O EXT

Agar Plate

Not stated

Inactive Inactive Inactive Inactive

Trichophytum gallinae Microsporum canis Microsporum gypseum Microsporum fulvum

T16253

Dried Bark Peru

Antiyeast Activity

ETOAC EXT

Agar Plate

1.0 mg/disc

Inactive Inactive

Candida albicans Saccharomyces cerevisiae

T16253

Dried Bark Peru

Antiyeast Activity

H2O EXT

Agar Plate

1.0 mg/disc

Inactive Inactive

Candida albicans Saccharomyces cerevisiae

T16253

Latex Colombia

Antiviral Activity

H20 EXT

Cell Culture

Not stated

Active Active

Virus - Cytomegalovirus Virus - Sindbis

AS1013

Fresh Latex South America

Antiviral Activity

Latex

Cell Culture

Not stated

Active Active

Virus - Respiratory Syncytial Virus - Influenza A

H14332

Dried Bark Peru

Antiviral Activity

ETOAC EXT

Cell Culture

LC50: 0.28 mcg/ml LC50: 100 mcg/ml

Active Inactive

Virus - Cytomegalovirus Virus - Sindbis (Infected host cells exposed to extract.)

T16253

Dried Bark Peru

Antiviral Activity

ETOAC EXT

Cell Culture

LC50: >100 mcg/ml

Inactive Inactive

Virus - Cytomegalovirus Virus - Sindbis (Virus exposed to extract before infecting host cells.)

T16253

Dried Bark Peru

Antiviral Activity

ETOAC EXT

Cell Culture

LC50: >100 mcg/ml

Inactive Inactive

Virus - Cytomegalovirus Virus - Sindbis (Infected host cells exposed to extract.)

T16253


IG = Intragastric



PO = Orally

SC = Subcutaneously

IM = Intramuscular

Biological Activities for Compounds in Sangre de Grado (Croton lechleri) Compound

Activity Tested For

Test Model

Dosage

Result

Taspine

Toxicity Assessment

PO Rat

LD50: 518 mg/kg

Active

Taspine

Carcinogenic Activity

External Mouse

0.2 mg/animal

Inactive

Dosing twice weekly for 17 months.

M26029

Taspine

Teratogenic Activity

Cell Culture

Not stated

Inactive

vs. rat embryo cultures

AS1006

Taspine

Embryotoxic Activity

Cell Culture

80 mcg/ml

Inactive

vs rat embryo cultures

AS1006

Taspine

Wound Healing Activity

Rat External

250 mcg/animal

Active

Had significantly greater mononuclear cellular infiltration over controls.

AS1007

Taspine


Rat External

250 mcg/animal

Active

Wound tensile strength increased at 5 & 7 days post surgery

AS1007

Taspine


Mouse External

ED50: 0.375 mg/kg

Active

M26029

Taspine


Human External

Not stated

Active

K15048

Taspine


In vivo In vitro

150-300 mcg/animal 0.50-0.4 mcg/ml

Active Active

Enhanced wound healing by increasing the autocrine of TGF-beta1 and EGF by fibroblasts.

AS1016

Taspine


Rat External

2 mg/ml

Active

Promoted skin wound healing, accelerated the growth of newly born capillaries and raised the production of protein and collagen in wound tissue.

AS1017

Taspine

Cytotoxic Activity

Cell Culture

IC50=0.39 mcg/ml IC50=0.17 mcg/ml

Active Active

KB cancer cells V-79 cancer cells

AS1008

Taspine

Cytotoxic Activity

Cell Culture

IC50=0.39 mcg/ml IC50=0.17 mcg/ml

Active Active

CA-9KB cancer cells. Hamster-Chinese V79

L04063 M30433

Taspine

Immune Enhancement Activity

Cell Culture

Not stated

Active

Enhanced phagocytosis in monocytes.

L26126

Taspine

Cell Growth Enhancement

Cell Culture

100 mcg/ml

Inactive

fibroblasts - foetal lung

AS1007

Taspine

Cell Migration Effect

Cell Culture

0.2 ng/ml

Active

fibroblasts - human

M26029


IG = Intragastric



PO = Orally


Ref # N00002

SC = Subcutaneously

IM = Intramuscular

Compound

Activity Tested For

Test Model

Dosage

Result


Ref #

Taspine

Anticomplement Activity

Cell Culture

IC50: 38 mcg/ml

Active

vs. CP complement system

L26126

Taspine

Anti-inflammatory Activiity

GI Rat GI Rat

100 mg/kg 20 mg/kg 20 mg/kg

Active Active Active

vs. carrageenan-induced pedal edema vs. adjuvant-induced arthritis vs. cotton pellet granuloma

A14041

Taspine

Anti-inflammatory Activiity

IG Rat

58 mg/kg 20 mg/kg 20 mg/kg


vs. carrageenin-induced pedal edema vs. cotton pellet-induced granuloma vs. adjuvant polyarthritis

N00002

Taspine

Antiviral Activity

Cell Culture

Not stated


Avian myeloblastosis Rauscher murine leukemia Simian sarcoma

K10864

Taspine

Antiviral Activity

Cell Cuture

Not stated

Active

Inhibited glucose-6-phosphate dehydrogenase in animal tumor viruses.

L00933

SP-303

Toxic Effect

IG Mouse

90 mg/kg

Inactive

SP-303

Toxic Effect

IG Monkey

> 200 mg/kg

Active

SP-303

Toxic Effect

IG Dog

100 mg/kg

Inactive

SP-303

Toxic Effect

IP Rat

30 mg/kg

Active

SP-303

Toxicity Assessment

IP Mouse IV Mouse IV Rat IP Rat IG Rat IV Dog

LD50: >50 mg/kg LD50: >100 mg/kg LD50: >50 mg/kg LD50: >100 mg/kg LD50: >300 mg/kg LD50: >18.9 mg/kg

Inactive

H14332

SP-303

Toxic Effect

IP Mouse

30 mg/kg

Inactive

H14332

SP-303


Human Oral

50 mg daily Not stated 2 gm daily 2 gm daily

Active Active Active Active

J16486 J17024 L05604 L06176

SP-303


IG Mouse

100 mg/kg

Active

L06695


IG = Intragastric



PO = Orally

H14332 CNS side effects, thrombocytopenia & histopathological side effects.

H14332 H14332

All animals died.

SC = Subcutaneously

K19993

IM = Intramuscular

Compound

Activity Tested For

Test Model

Dosage

Result


Ref #

SP-303

Antiviral Activity

Cell Culture

ED50: 13.6 mcg/ml ED50: 6.7 mcg/ml ED50: 7.0 mcg/ml ED50: 13.7 mcg/ml ED50: 3.0 mcg/ml ED50: 50.0 mcg/ml

Active Active Active Active Active Active

Respiratory syncytial A Respiratory syncytial B Influenza A Influrenza B Parainfluenza Type I Parainfluenza Type 3

H14332

SP-303

Antiviral Activity

Cell Culture

ED50: 79.0 mcg/ml ED50: 3.0 mcg/ml ED50:14.0 mcg/ml ED50: 7.0 mcg/ml ED50: 14.0 mcg/ml

Active Active Active Active Active

Parainfluenza Type 3 Parainfluenza Type 1 Respiratory syncytial Influenza A Influenza B

K10599

SP-303

Antiviral Activity

IP Rat IP Rat IG Rat IG Rat

ED50: 3.0 mcg/ml ED50: 3.0 mcg/ml ED50: 10.0 mcg/ml ED50: 10.0 mcg/ml


Respiratory syncytial Parainfluenza Type 3 Respiratory syncytial Parainfluenza Type 3

K10599

SP-303

Antiviral Activity

Cell Culture

Not stated

Inactive Inactive

Adenovirus 5 Measles virus

H14332 K11125

SP-303

Antiviral Activity

IV Monkey IG Monkey

5.0 mg/kg 30.0 mg/kg

Active Active

Respiratory syncytial

H14332

SP-303

Antiviral Activity

IP Rat IG Rat

1 mg/kg 1 mg/kg

Active Active


H14332

SP-303

Antiviral Activity

IP Mouse IG Mouse

9 mg/kg 9 mg/kg

Active Active

Influenza A

H14332

SP-303

Antiviral Activity

IP Ferret

10 mg/kg

Inactive

Influenza A

H14332

SP-303

Antiviral Activity

Aerosol Rat

1 mg/kg

Active


H14332

SP-303

Antiviral Activity

IP Rat

10 mg/kg

Active

Parainfluenza Type 3

H14332

SP-303

Antiviral Activity

Vaginal Guinea Pig

30%

Inactive

Herpes Simplex I

H14332

SP-303

Antiviral Activity

IP Mouse IG Mouse Vaginal Mouse Vaginal Guinea Pig

30 mg/kg 90 mg/kg 10% 10%


Herpes Simplex 2

H14332


IG = Intragastric



PO = Orally

SC = Subcutaneously

IM = Intramuscular

Compound

Activity Tested For

Test Model

Dosage

Result


Ref #

SP-303

Antiviral Activity

IP Rat IP Rat

1.0 mg/kg 3.4 mg/kg

Acive Active

Respiratory syncytial Parainfluenza Type 3

K10657

SP-303

Antiviral Activity

Cell Culture

ED50: 9 mcg/ml ED50: 7 mcg/ml ED50: 11 mcg/ml ED50: 3 mcg/ml ED50: 98 mcg/ml ED50: 5 mcg/ml

Active Active Active Active Active Active

Influenza A - Taiwan Influenza A - Shanghai Influenza B - Yamagata Parainfluenza Type 1 Parainfluenza Type 3 Respiratory syncytial

K11125

SP-303

Antiviral Activity

Vaginal Mouse IG Mouse IP Mouse

10% 540 mg/kg 30 mg/kg


Herpes Simplex 2

K13678

SP-303

Antiviral Activity

Cell Culture

IC50: 1 to 5 mmol IC50: 1 to 7 mmol

Active Active

Herpes Simplex 1 (various strains) Herpes Simplex 2 (various strains)

K13678

SP-303

Cytotoxic Activity

Cell Culture

Various

Inactive Inactive Inactive Inactive Inactive

Cells-Vero CA-A549 CA-HEP-2 Canine-Kidney Glioma-Human-ONS-12

K14332 K11125

SP-303

Cytotoxic Activity

Cell Culture

IC50: 4.0 mmol IC50: 3.0 mmol

Active Active

Hep2 Cells Cells-Vero

K13678


IG = Intragastric



PO = Orally

SC = Subcutaneously

IM = Intramuscular

LITERATURE CITED A14041

ANTI-INFLAMMAT ION CO MPO SITIONS CO NTAINING T ASPINE OR A CID SALTS T HEREO F AND M ETHO D OF U SE. PERSINOS,GJ: PATENT-US-3,694,557 : 6PP-. (1972) (AMAZON M ATL DRUG CO SOM ERVILLE NJ USA)

H07769

POLYP HEN OLIC C OM POU NDS FRO M CR OT ON LECH LERI. CAI,Y: EVANS,J: ROBE RTS ,MF: PHILLIPSON ,JD: ZENK,MH : GLEBA,YY: PHYTOCHEMISTRY 30 6: 2033-2040 (1991) (DEPT PHARMACOG SCH PHARM UNIV LONDON LONDON W C1N 1AX ENGLAND)

H11766

DITERPENES FROM CROTON LECHLERI. CAI,Y: CHEN,ZP: PHLLIPSON,J: PHYTOCHEMISTRY 32 3: 755-760 (1993) (DEPT PHARMACOG SCH PHARM UNIV LONDON LONDON W C1N 1AX ENGLAND)

H14225

CLERO DANE D ITERPENO IDS FROM CRO TON LECHLER I. CAI,Y: CHEN ,ZP: PHILLIPSON,JD: PHYTOC HEMISTR Y 34 1: 265-268 (1993) (DEP T PH ARM ACO G S CH PHA RM UN IV LON DO N LO ND ON W C1N 1AX ENG LAN D)

H14332

SP-303 , AN AN TIVIRA L OL IGO ME RIC P RO ANT HO CYA NIDIN FRO M T HE L ATE X O F CR OT ON LEC HLE RI (SAN GR E DE DR AG O). UBILLAS,R: JOLAD,SD: BRUENING,RC: KERNAN,MR: KING,SR: SESIN,DF: BARRETT,M: STODDART,CA: FLASTER,T: KUO,J: AYALA,F: MEZA,E: CASTANEL,M: MC MEEKIN, D: ROZHON,E: TEMPESTA,MS: BARNARD,D: HUFFMAN,J: SMEE,D: SIDW ELL,R: SOIKE,K: BRAZIER,A: SAFRIN,S: ORLANDO,R: KENNY,PTM: BEROVA,N: NAKANISHI,K: PHYTOMEDICINE 1 2: 77-106 (1994) (SHAMAN PHAR M SAN FRANCISCO CA 94080 USA)

H22027

CROT ON RUIZIANUS: PLATELET PROAGGREG ATING ACTIVITY OF TW O NEW PREGNANE G LYCOIDES. PIACENTE,S: BELISARIO,MA: DEL CAS TILLO ,H: PIZZA ,C: DE F EO ,V: J NAT PRO D 61 3: 318 -322 (1998 ) (DIPT S CI FAR M PIA ZZA EMA NU EL SA LER NO ITALY)

J16430

ISOLATION OF A DIHYDROBENZOFURAN LIGNAN FROM SOUTH AMERICAN DRAGON'S BLOOD (CROTON SPP.) AS AN INHIBITOR OF CELL PRO LIFERATION. PIETERS,L: DE BRUYNE,T: CLAEYS,M: VLIETINCK,A: CALOM ME,M: VANDEN BERGH E,D: J NAT PROD 56 6: 899-906 (1993) (DEPT PHARM SCI UNIV ANTWERP ANTWERP B-2610 BELGIUM)

J16486

SP-303: A NEW TREATM ENT FOR AIDS-ASSOCIATED DIARRHEA.; HOLOD NIY,M: KOCH,J: MISTAL,M: SCHMIDT,JM: O'HANLEY,P: PENNINGTON ,J: PORTER,S: ABSTR XII W ORLD AIDS CONFER ENCE GENEVA JULY 1998 (1998) 1998 pp. SCRIPPS INST OCEANO GRAPHY INST MARINE RESOUR CES LA JOLLA CA 92037 USA

J17024

RECENT NATURAL PRODUCTS BASED DRUG DEVELOPMENT: A PHARMACEUTICAL INDUSTRY PERSPECTIVE.; SHU,YZ: J NAT PROD (1998) 61 (8) pp. 1053-1071; SQUIBB PHARMACEUT RES INST BRISTOL-MYERS W ALLINGFO RD CT 06492 USA

J19239

EFFECTS OF SAN GRE DE DR AGO FRO M CRO TON LECH LERI MUELL.-ARG. ON THE PROD UCTION OF T HE PRODU CTION OF ACT IVE OXYGEN RADICALS. DESMARCHELIER,C: SCHAUS,FW : COUSSIO,J: CICCA,G: J ETHNOPHARMACOL 58 2: 103-108 (1997) (CATEDRA MICR OB IL INDU ST B IOT FAC FAR M BIO QU IM UN IV BUE NO S AIRE S AR GE NT INA)

K10599

ELUCIDATION OF A POLYPHENOLIC POLYMER W ITH ANTIVIRAL ACTIVITY AGAINST MYXO- AND PARAMYXOVIRUSES.; W YDE,PR: MEYERSON,LR: AMBROSE,MW : PFEIFER,JB: VOSS,TG: GILBERT,BE: ANTIVIRAL RES SUPPL (1991) 1 pp. 67-.BAYLOR COLL MED HOUST ON TX USA

22

K10600

MODE OF ACTION OF SP-303 AGAINST RESPIRATORY SYNCYTIAL VIRUS (RSV).; BARNARD,DL: HUFFMAN,JH: NELSON,RM: MORR IS,JLB: GESSAMAN,AC: SIDW ELL,RW : MEYERSON,LR: ANTIVIRAL RES SUPPL (1991) 1 pp. 138-. UTAH STAT E UNIV INST ANTIVIRAL RES LOGAN U T USA

K10657

THE ANTIVIRAL ACTIVITY OF SP-303, A NATURAL POLYPHENOLIC POLYMER, AGAINST RESPIRATORY SYNCYTIAL AND PARAINFLUEN ZA TYPE 3 VIRUS IN CO TTO N RAT S.; W YDE,PR: AMBRO SE,MW : MEYERSON ,LR: GILBERT,BE: ANTIVIRAL RES (1993) 20 (2) pp. 145-154. BAY COLL MED DEPT MICRO BIOL IMMUN OL HOUST ON TX 77030 USA

K10718

IN VITRO AND IN VIVO BIOLOGICAL ACTIVITY OF SOUTH AMERICAN DRAGON'S BLOOD AND ITS CONSTITUENTS. PIETERS,L: DE BR UYNE ,T: M EI,G : LEM IER E,G : VAND EN BERG HE ,D: VLIET INC K,AJ: PL AN TA ME D S UP PL 58 1: A58 2-A583 (199 2) (D EPT P HA RM SC I UNIV ANTWERP ANTWERP B-2610 BELGIUM)

K10864

SEARCH FOR N EW ANTIVIRAL AGEN TS OF PLANT O RIGIN. KAIJ-A-KAMB,M: AMOR OS,M: GIRRE,L: PHARM AC TA HELV (1992) 67 (5/6) pp. 130-147; CHEMICAL ABSTRACTS 118 93637 F FAC PHARM LAB PHARMACOGN RENNES F 35043 FRANCE

K11125

IN VITRO EVALUATION OF THE ANTIVIRAL ACTIVITY OF SP-303, AN EUPHORIBACEAE VIRUSES. W YDE,PR: MEYERSON,LR: GILBERT,BE: DRUG D EV RES (1993) 28 (4) pp. 467-472 ; BAYLOR COLL MED DEPT MICOBIOL IMMUNOL HO USTON TX USA

K12672

MODE OF INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS BY A PLANT FLAVONOID, SP-303. BARNARD,DL: HUFFMAN,JH: MEYERS,LR: SIDW ELL,RW : CHEMOTHER APY (1993) 39 (3) pp. 212-217 UTAH STATE UNIV INST ANTIYIRAL RES LOGAN USA

K13678

ANTIHERPES VIRUS ACTIVITY AND MODE OF ACTION OF SP-303, A NOVEL PLANT FLAVONOID. BARNARD,DL: SMEE,DF: HUFFMAN ,JH: MEYERSON,LR: SIDW ELL,RW : CHEMOTHER APY (1993) 39 (3) pp. 203-211 UTAH STATE UNIV INST ANTIVIRAL RES LOGAN UT USA

K14558

INFLUENZA VIRUS-INHIBITORY EFFECTS OF INTRAPERITONEALLY AND AEROSOL-ADMINISTERED SP-303, A PLANT FLAVONOID. SIDW ELL,RW : HUFFMAN,JH: MOSCO N,BJ: W ARREN,RP: CHEMOTHER APY(BASEL) (1994) 40 (1) pp. 42-50.; UTAH STAT E UNIV INST ANTIYIRAL RES LOGAN UT USA

K14559

SP-303 SMALL PARTICLE AEROSOL TREATMENT OF INFLUENZA A VIRUS INFECTION IN COTTON RATS. GILBERT,BE: W YDE,PR: W ILSON,SZ: MEYERSON,LR: ANTIVIRAL RES (1993) 21 (1) pp. 37-45 BAYLOR COLL MED DEPT MICROBIOL IMMUNOLY HOUSTON TX 77030 USA

K15048

W OUND -HEALING CO MPOSITION.; LEW IS: ET AL: PATENT-US-5,156,847 (1992) 1992 pp. 2-7 PATENT USA

K18768

STU DIES O N TH E ANT I-TUMO UR, AN TI-BACT ERIAL, AND W OU ND-H EALING PRO PERT IES OF D RAG ON 'S BLOO D. CHE N,ZP: CAI,Y: PHILLIPSON,JD: PLANTA MED 60 6: 541-545 (1994) (DEPT PHARMACOG SCH PHARM UNIV LONDON LONDON W C1N 1AX ENGLAND)

K19993

INFLUENZA VIRUS-INHIBITORY EFFECTS OF INTRAPERITONEALLY AND AEROSOL-ADMINISTERED SP-303, A PLANT FLAVONOID. SIDW ELL,RW : HUFFMAN,JH: MOSCO N,BJ: W ARREN,RP: CHEMOTHER APY (1994) 40 (1) pp. 42-50 UTAH STATE UN IV INST ANTIVIRAL RES LOGAN U T USA

23

K22608

IN VIVO WOUND HEALING ACTIVITY OF DRAGON'S BLOOD (CROTON SPP.), A TRADITIONAL SOUTH AMERICAN DRUG, AND ITS CONST ITUENTS. PIETERS,L: DE BRUYNE,T: VAN POEL,B: VINGERH OETS,R: TOTTE,J: VANDEN BERGHE,D: VLIETINCK: PHYTOMEDICINE 2 1: 17-22 (1995) (DEPT PHARM SCI UNIV ANTWERP ANTWERP B-2610 BELGIUM)

K28263

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